QTAIM Approach Research Articles

FT-IR spectroscopy, intra-molecular C−H⋯O interactions, HOMO, LUMO, MESP analysis and biological activity of two natural products, triclisine and rufescine: DFT and QTAIM approaches

The present study deals with two natural products, triclisine and rufescine which are extracted from the Amazonian wines but ubiquitous in nature. The quantum chemical density functional method at B3PW91/6-311+G(d,p) level is used to obtain the equilibrium geometries of these molecules. The quantum theory of atoms-in-molecule approach is employed to study various intra-molecular C−H⋯O interactions within these molecules. We have also performed vibrational analyses of triclisine and rufescine at their equilibrium geometries and presented the complete assignments of the significant vibrational modes. The calculated vibrational frequencies are shown to be in perfect agreement with the experimentally observed FTIR spectra of molecules under study. In addition, the electronic properties of these molecules are also discussed with the help of HOMO–LUMO and MESP surfaces and a number of electronic as well as thermodynamic parameters are calculated which are closely related to their chemical reactivity and reaction paths. The biological activities of both molecules have also been predicted which highlight their pharmacological importance.

The Zintl Phase Cs7NaSi8 – From NMR Signal Line Shape Analysis and Quantum Mechanical Calculations to Chemical Bonding

AbstractPowder samples as well as red and transparent single crystals of the Zintl phase Cs7NaSi8 were synthesized and characterized by means of X‐ray diffraction and differential thermal analysis. Cs7NaSi8 was found to be isotypic to the recently reported phase Rb7NaSi8. It crystallizes in the Rb7NaGe8 structure type forming trigonal pyramidal Si44– anions. Two unique environments of the cations are observed, a linear arrangement [Na(Si4)2]7– with short Na–Si distances of 3.0 Å and a Cs2 atom coordinated by six Si44– anions with long Cs–Si distances of 4.2 Å. The bonding situation was investigated by a combined application of 29Si, 23Na, and 133Cs solid‐state NMR spectroscopy and quantum mechanical calculations of the NMR coupling parameters. In addition the electronic density of states (DOS), the electron localizability indicator (ELI) and the atomic charges using the QTAIM approach were studied. Good agreement of the calculated and experimental values of the NMR coupling parameters was obtained. An anisotropic bonding situation of the silicon atoms is indicated by the chemical shift anisotropy being similar to Rb7NaSi8. Confirmation is given by the observation of one lone‐pair‐like feature for each silicon atom and two types of two‐center Si–Si bonds using the ELI. Calculation and NMR spectroscopic determination of the 23Na and 133Cs electric field gradients prove anisotropies of the charge distribution around the cations. Due to the similar values for the Na atoms in M7NaSi8 (M = Rb, Cs) equal bonding situations can be concluded. The much larger anisotropy of the charge distribution of the Cs atoms can be addressed as the main difference to Rb7NaSi8.

Halogen bonding in iron(II) and cobalt(II) tris(dichloroglyoximates)

The understanding of the interplay between intermolecular strong and weak interactions requires approaches that are able to identify and quantify all of them, and are applicable to as large number of objects as possible. The QTAIM approach [1] nicely meets the first criteria. Less rigorous approaches, such as the Stockholder [2] and the Voronoi [3] partitioning have the second advantage. The latter can also give qualitative, quantitative and visual representation of intermolecular interactions. We compared how all these approaches would perform for two polymorphs of Fe(Cl2Gm)3(BCH3)2 (monoclinic C (1a), and less stable monoclinic P (1b)) and Co(Cl2Gm)3(BCH3)2 (2) isostructural with 1b (Cl2Gm = dichloroglyoximate). The Voronoi and Stockholder partitionings showed that three fourths of molecular surfaces were attributed to Cl...X (X = Cl, O, N) and C-H...Cl bonds. According to the QTAIM theory, each chlorine atom takes part in at least four intermolecular contacts. The Voronoi tessellation was found to be valid for determinating of the graph of intermolecular bonding. Indeed, in the isostructural 1b and 2 the sets of weak interactions do not coincide due to various conformations of iron- and cobalt-containing clathrochelate cages. Nevertheless, the resulting graph of intermolecular bonding (the gpu-x net) is the same. Qualitative (for all three approaches) and quantitative (for two partitionings) correlation for various methods was demonstrated. This study was supported by the Council of the President of the Russian Federation (MK-5181.2013.3 and MD- 3589.2014.3).

Topological reaction sites – very strong chalcogen bonds

The analysis of interactions in complexes of S(CN)2, Se(CN)2, SFCl and SeFCl with F(-) and Cl(-) anions is performed here. The sulphur and selenium atoms act in these complexes as Lewis acid centres interacting with fluorine and chlorine anions. The arrangement of sub-units in complexes is in agreement with the σ-hole concept; particularly it is a result of contacts between positive and negative electrostatic potential sites. The interactions in complexes analyzed may be classified as very strong charge assisted chalcogen bonds and they possess numerous characteristics typical for covalent bonds. Even in the case of complexes of SFCl and SeFCl, i.e. SFCl2(-) and SeFCl2(-), the trivalency of the chalcogen atom is observed. The calculations were carried out at the MP2(full)/aug-cc-pVTZ level of approximation, the analyses were performed with the use of the Natural Bond Orbital (NBO) method, the Quantum Theory of 'Atoms in Molecules' (QTAIM) and the Electron Localization Function (ELF) approach. The results obtained by these methods are in agreement giving the consistent picture of the complexes' configurations and their electron charge distribution. The QTAIM and ELF approaches allow us to predict for S(CN)2, Se(CN)2, SFCl and SeFCl molecules the directions of nucleophilic attack. They are in line with the prediction based on the σ-hole concept. The Symmetry Adapted Perturbation Theory (SAPT) approach was also applied.

A comparative computational study on molecular structure, NBO analysis, multiple interactions, chemical reactivity and first hyperpolarisability of imatinib mesylate polymorphs using DFT and QTAIM approach

Imatinib, a phenylaminopyrimidine compound is a therapeutic drug for treatment of chronic myelogeneous leukaemia and gastrointestinal stromal tumours. It is well known that imatinib mesylate (ImM) exists in two polymorphic forms α and β. In this work, a computational study on molecular properties of ImM polymorphs is presented using density functional theory, B3LYP functional and 6-311G(d,p) as basis set. Natural bond orbital analysis is carried out to investigate the various conjugative and hyperconjugative interactions within the molecule and their second-order stabilisation energy (E(2)). The local nucleophilic reactivity descriptors such as Fukui functions (), local softness () and electrophilicity indices () analyses are carried out to determine the reactive sites within the molecule. To determine strength and nature of intra- and intermolecular interactions, topological parameters as electron density (ED) (ρBCP), Laplacian of ED (▽2ρBCP) and total electron energy density (HBCP) at bond critical points have been analysed by ‘quantum theory of atoms in molecules’ in detail. The computed first hyperpolarisability (β0) for both forms of ImM molecule (10.927 and 10.354 × 10− 30 esu) suggests that the investigated molecule is an attractive object in future for non-linear optical properties. Molecular electrostatic potential surface of ImM has been mapped to predict the inhibitory activity and binding affinity with a panel of protein tyrosine kinases.

Atomistic nature of the DPT tautomerisation of the biologically important C·C* DNA base mispair containing amino and imino tautomers of cytosine: a QM and QTAIM approach

A theoretical study of tautomerisation of the biologically important cytosine·cytosine* (C·C*) DNA mismatch with a propeller-like structure (|C4N3N3C4| = 32.4°; C1 symmetry) and cis-oriented N1H glycosidic bonds, formed by the amino and imino tautomers of the C nucleobase, via the asynchronous concerted double proton transfer (DPT) along two H-bonds through the transition state (TSC·C*↔C*·C) (|C4N3N3C4| = 48.5°; C1 symmetry) into the C*·C mispair was carried out for the first time. It was established that the C·C*/C*·C DNA base mispair is associated by the antiparallel N4H···N4 (6.66 kcal mol(-1)), N3H···N3 (6.47 kcal mol(-1)) H-bonds and the O2···O2 van der Waals (vdW) contact (0.33 kcal mol(-1)), while the zwitterionic TSC·C*↔C*·C is stabilized by the parallel N4(+)H···N4(-) (13.55 kcal mol(-1)), N3(+)H···N3(-) (13.20 kcal mol(-1)) H-bonds and the O2(+)···O2(-) vdW contact (0.60 kcal mol(-1)). It was shown that the C·C* ↔ C*·C tautomerisation via the DPT is assisted by the O2···O2 vdW contact, that in contrast to the two others N4H···N4 and N3H···N3 H-bonds exists along the entire intrinsic reaction coordinate (IRC) range. The positive values of the Grunenberg's compliance constants (30.919 and 21.384 Å mdyn(-1) for C·C*/C*·C and TSC·C*↔C*·C, respectively) indicate that the O2···O2 vdW contact is a stabilizing closed-shell interaction. It was found that the middle N3H···N3 H-bond is anti-cooperative with the upper N4H···N4 H-bond and cooperative with the lower O2···O2 vdW contact. The 9 key points, which can be considered as electron-topological "fingerprints" of the asynchronous concerted C·C* ↔ C*·C tautomerisation process via the DPT were revealed along the IRC and examined in detail. It was shown that the C·C*/C*·C base mispair is a thermodynamically and dynamically stable structure. Its lifetime is equal to 1.53 × 10(-7) s at the MP2/cc-pVQZ//B3LYP/6-311++G(d,p) level of theory in vacuum. All 6 low-frequency intermolecular vibrations are able to develop during this time span.

Phenylvinylcobalamin: an alkenylcobalamin featuring a ligand with a large trans influence

Cob(I)alamin reacts with phenylacetylene to produce two diastereomers in which the organic ligand is coordinated to the upper (β) and lower (α) face of the corrin ring, respectively. The isomers were separated chromatographically and characterised by ESI-MS and, in the case of the β isomer, by (1)H and (13)C NMR. Only the β isomer crystallised and its molecular structure, determined by X-ray diffraction, shows that the organic ligand coordinates Co(III) through the β carbon of the phenylvinyl ligand. The Co-C bond length is 2.004(8) Å while the Co-N bond length to the trans 5,6-dimethylbenzimidazole (dmbzm) base is 2.217(8) Å, one of the longest Co-Ndmbzm bond lengths known in an organocobalamin. Unlike benzylcobalamin (BzCbl), phenylvinylcobalamin (PhVnCbl) is stable towards homolysis. DFT calculations (BP86/TZVP) on model compounds of BzCbl and PhVnCbl show that the Co-C bond dissociation energy for homolysis to Co(II) and an organic radical in the former is 8 kcal mol(-1) lower than in the latter. An analysis of the electron density at the Co-C bond critical point using Bader's QTAIM approach shows that the Co-C bond in PhVnCbl is shorter, stronger and somewhat more covalent than that in BzCbl, and has some multiple bond character. Together with calculations that show that the benzyl radical is more stable than the phenylvinyl radical, this rationalises the stability of PhVnCbl compared to BzCbl. The phenylvinyl ligand has a large trans influence. The pKa for deprotonation of dmbzm and its coordination by the metal in β-PhVnCbl is 4.60 ± 0.01, one of the highest values reported to date in cobalamin chemistry. The displacement of dmbzm ligand by CN(-) in β-PhVnCbl occurs with log K = 0.7 ± 0.1; the trans influence order of C-donor ligands is therefore CN(-) < CCH < CHCH2 = PhVn < Me < Et.

Low-energy conformers of pamidronate and their intramolecular hydrogen bonds: a DFT and QTAIM study

Extensive DFT and ab initio calculations were performed to characterize the conformational space of pamidronate, a typical pharmaceutical for bone diseases. Mono-, di- and tri-protic states of molecule, relevant for physiological pH range, were investigated for both canonical and zwitterionic tautomers. Semiempirical PM6 method were used for prescreening of the single bond rotamers followed by geometry optimizations at the B3LYP/6-31++G(d,p) and B3LYP/6-311++G(d,p) levels. For numerous identified low energy conformers the final electronic energies were determined at the MP2/6-311++G(2df,2p) level and corrected for thermal effects at B3LYP level. Solvation effects were also considered via the COSMO and C-PCM implicit models. Reasonable agreement was found between bond lengths and angle values in comparison with X-ray crystal structures. Relative equilibrium populations of different conformers were determined from molecular partition functions and the role of electronic, vibrational and rotational degrees of freedom on the stability of conformers were analyzed. For no level of theory is a zwitterionic structure stable in the gas-phase while solvation makes them available depending on the protonation state. Geometrically identified intramolecular hydrogen bonds were analyzed by QTAIM approach. All conformers exhibit strong inter-phosphonate hydrogen bonds and in most of them the alkyl-amine side chain is folded on the P-C-P backbone for further hydrogen bond formation.

The Silicides M4Si4 with M = Na, K, Rb, Cs, and Ba2Si4 – NMR Spectroscopy and Quantum Mechanical Calculations

AbstractThe Zintl phases M4Si4 with M = Na, K, Rb, Cs, and Ba2Si4 feature a common structural unit, the Si44– anion. The coordination of the anions by the cations varies significantly. This allows a systematic investigation of the bonding situation of the anions by 29Si NMR spectroscopy. The compounds were characterized by powder X‐ray diffraction, differential thermal analysis, magnetic susceptibility measurements, 23Na, 29Si, 87Rb, 133Cs NMR spectroscopy, and quantum mechanical calculation of the NMR coupling parameter. The chemical bonding was investigated by quantum mechanical calculations of the electron localizability indicator (ELI). Synthesis of the compounds results for all of them in single phase material. A systematic increase of the isotropic 29Si NMR signal shift with increasing atomic number of the cations is observed by NMR experiments and quantum mechanical calculation of the NMR coupling parameter. The agreement of experimental and theoretical results is very good allowing an unambiguous assignment of the NMR signals to the atomic sites. Quantum mechanical modelling of the NMR shift parameter indicates a dominant influence of the cations on the isotropic 29Si NMR signal shift. In contrast to this a negligible influence of the geometry of the anions on the NMR signal shift is obtained by these model calculations. The origin of the systematic variation of the isotropic NMR signal shift is not yet clear although an influence of the charge transfer estimated by calculation using the QTAIM approach is indicated.

Multicenter delocalization indices vs. properties of the electron density at ring critical points: A study on polycyclic aromatic hydrocarbons

Six-center delocalization indices, 6-DI’s, computed within Mulliken and QTAIM approaches, and properties of the electron density at ring critical points, RCP’s, (electron density and its Laplacian) are studied for a series of 27 polycyclic aromatic hydrocarbons. Both approaches reflect the same trends for the local aromaticity of benzenoid rings. Moreover, there is a linear correlation between the natural logarithm of 6-DI’s and RCP properties. The RCP properties calculated at the DFT level indicate the local aromaticity decreases from outer to inner rings in polyacenes. This contradicts previous results obtained at HF level and supports the conclusions of multicenter indices.